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Ascorbate prevents sepsis‐induced reduction in arteriolar conducted vasoconstriction in the mouse cremaster muscle
Author(s) -
McKin Rebecca L,
Lidington Darcy,
Tyml Karel
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a276
Subject(s) - cremaster muscle , vasoconstriction , reduction (mathematics) , sepsis , microcirculation , cardiology , medicine , chemistry , geometry , mathematics
We showed that increased nNOS activity and resultant NO production in the mouse cremaster muscle are the key factors responsible for the reduction in arteriolar conducted vasoconstriction during sepsis. In the present study, we hypothesized that an ascorbate bolus administered at the time of the onset of sepsis (cecal ligation and perforation, CLP) prevents the increase in NOS activity at 24 h post‐CLP and the subsequent deficit in conduction. Arterioles were locally stimulated with KCl and the ratio of conducted (500 μm upstream) to local constriction was used as an index of the conducted response (CR 500 ). Sepsis (24 h) reduced CR 500 from 0.75 to 0.20, and increased cNOS (i.e. eNOS + nNOS) activity from 70 to 95 pmol/mg/hr. Ascorbate bolus (200 mg/kg, tail vein injection at 0 h) prevented both the increase in cNOS activity (67 pmol/mg/hr) and the conduction deficit (CR500 = 0.64) at 24 h post‐CLP. Further, ascorbate bolus injection at 23 h post‐CLP restored conduction (CR 500 = 0.71) at 24 h. Superfusion of the cremaster muscle with MnTBAP (10 μM, superoxide scavenger, 20 min) at 24 h had no effect at this time point. Therefore, both the immediate and delayed ascorbate boluses prevented/restored the arteriolar conduction deficit in septic mice, possibly by preventing sepsis‐induced increase in nNOS activity in the cremaster muscle at 24 h. We suggest that ascorbate may be used as a potential therapeutic treatment to restore microvascular function in septic patients. (Supported by the CIHR and HSFO.)